According to the CDC, more than 1 billion people, or one-sixth of the world’s population, is suffering from one or more Neglected Tropical Diseases with many of these diseases affecting the poorest populations in the developing world. Our lab focuses on the parasitic disease from Leishmania infection. Cutaneous leishmaniasis has a wide spectrum of clinical manifestations, ranging from self-healing to chronic debilitating disease. Throughout the world, there are 1 billion people living in endemic areas at risk of infection. Annually, about 1 million new cases are detected in tropical and subtropical regions with major foci in Asia and South America. Presently, drugs against the parasite are extremely toxic and there is no vaccine. Control of the parasite is dependent upon the activation of macrophages, leading to production of nitric oxide and reactive oxygen species. However, even when an appropriate adaptive immune response develops and parasites are controlled, cutaneous lesions often persist suggesting the inflammatory response can drive pathology. Therefore, the goal of our lab is to define the factors that control both lesion development and resolution which will be important in developing novel therapies for patients with the disease.

At the site of Leishmania infection, there is a massive infiltration of immune cells and dramatic changes in the vasculature. During infection, new blood vessels form which bring immune cells to the site of infection. Similarly, the lymphatic network also expands to allow these recruited cells to drain back into circulation leading to resolution of the inflammation. In order to characterize the vascular remodeling that occurs during infection, we use a mouse model to manipulate the cells and pathways, such VEGF-A/VEGFR-2 signaling, that are involved in the formation of new vessels. We combine a variety of cellular and molecular techniques, including flow cytometry, microscopy and imaging to address the role of the immune response. Furthermore, we are interested in evaluating the pathways associated with vascular remodeling since they may mediate immune cell infiltration and lesion resolution influencing the severity of disease. We hope the results from our work will provide novel strategies that target the vasculature to reduce the pathology seen in Leishmania patients with non-healing lesions, but also those suffering from other chronic inflammatory diseases and cancer.